Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5)

Abstract

Objective: To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks.

Research design and methods: This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented.

Results: The mean HbA1c changes to 52 weeks were (least squares mean ± SE): -1.10 ± 0.06% (-12.0 ± 0.7 mmol/mol), -0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and -0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (-3.03 ± 0.22 kg) and dulaglutide 0.75 mg (-2.60 ± 0.23 kg) compared with sitagliptin (-1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting.

Conclusions: Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Study design (A) and patient disposition (B). All patients underwent a metformin run-in period that lasted up to 11 weeks, to be continued for the duration of the study; other OAMs were discontinued. Seven doses of dulaglutide were evaluated in the dose-finding portion along with sitagliptin and placebo. At dose selection, dulaglutide 1.5 and 0.75 mg were selected for further evaluation. Only patients assigned to selected dulaglutide doses and comparators continued forward in the study. Placebo-treated patients continued until week 26 and were then switched to sitagliptin for blinding purposes. aRandomization. bPrimary end point. cFinal end point. dThe placebo period lasted for 26 weeks followed by a switch to sitagliptin to keep the arm blinded.

Figure 2

Efficacy and safety measures through the treatment period. A: Change in HbA1c from baseline at 26 and 52 weeks, ANCOVA LOCF. B: HbA1c over time, MMRM. C: Percentage of patients achieving HbA1c targets at 26 and 52 weeks. D: Change in FPG over time, MMRM. E: Change in weight over time, MMRM. Data presented are LS mean ± SE. ††P < 0.001, superiority vs. sitagliptin; ‡‡P < 0.001, superiority vs. placebo; #, *P < 0.05 vs. sitagliptin and placebo, respectively; ##, **P < 0.001 vs. sitagliptin and placebo, respectively.